Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus response to iron.

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af), the commonest bacterium and fungus in compromised host airways, compete for iron (Fe). The Pseudomonas quinolone signal (PQS), a Pa quorum sensing molecule, also chelates Fe, and delivers Fe to the Pa cell membrane using Pa siderophores. In models of Af biofilm formation or preformed biofilms, PCIS inhibited Af in a low Fe environment. Af Delta sidA (mutant unable to produce siderophores) biofilm was more sensitive to PUS inhibition than wild-type (WT), as was planktonic Af Delta sidA growth. PUS decreased WT Af growth on agar. All these inhibitory actions were reversed by Fe. The Pa siderophore pyoverdin, or Af siderophore inhibitor celastrol, act cooperatively with PUS in Af inhibition. These findings all indicate PUS inhibition is owing to Fe chelation. Remarkably, in high Fe environments, PUS enhanced Af biofilm at 1/100 to 1/2000 Fe concentration required for Fe alone to enhance. Planktonic Af growth, and on agar, Af conidiation, were also enhanced by POS+Fe compared to Fe alone. In contrast, neither Af Delta sidA biofilm, nor planktonic Af Delta sidA, were enhanced by PQS-Fe compared to Fe. When Af siderophore ferricrocin (FC),+PQS, were added to Af Delta sidA, Af was then boosted more than by FC alone. Moreover, FC+PQS+Fe boosted Af Delta sidA more than Fe, FC, FC+Fe, PQS+FC or PQS+Fe. Thus PQS-Fe maximal stimulation requires Af siderophores. PQS inhibits Af via chelation under low Fe conditions. In a high Fe environment, PUS paradoxically stimulates Af efficiently, and this involves Af siderophores. PUS production by Pa could stimulate Af in cystic fibrosis airways, where Fe homeostasis is altered and Fe levels increase, supporting fungal growth.